Diabetes mellitus alters the function of the intestinal absorptive cell in many ways. There is enhancement of active transport systems for hexoses, amino acids, bile salts, and sodium with kinetic changes suggestive of increased membrane "carriers". In addition there are increased total and specific activities of a number of membrane-bound hydrolases including sucrase, maltase, lactase, alkaline phosphatase, and leucylnaphthylamidase. We have found that the increased activity of these membrane glycoproteins induced by diabetes is not accompanied by increases in electrophoretically separated membrane proteins. This observation suggests an additional regulatory mechanism for these glycoproteins which does not involve protein synthesis or degradation; since immunologically identical active and inactive forms of at least one of them have been found by others, our observations indicate that the diabetic brush border contains a diminished quantity of inactive proteins and an increased quantity of active proteins. We propose to quantitate both active and inactive forms of one glycoprotein enzyme to determine the relationships of the two forms in the diabetic brush border and to study their relationships during the development of enzyme activity that occurs during cell differentiation in the villus. This will be done by enzymatic analysis and immunoprecipitation. We will ultimately purify both enzyme forms to study their differences; since diabetes is known to alter the carbohydrate moieties of other glycoproteins, we will initially study the carbohydrate composition of the two enzyme forms because of the possibility that alterations in the carbohydrate composition of the proteins affect their function. In addition we will determine if the increased transport function of the diabetic absorptive cell is related to apical membrane changes as we believe. This will be done by studying transport into isolated membrane vesicles which contain no energy source.